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1 including islet amyloid polypeptide (IAPP or amylin).
2 type 2 diabetes) with a known inhibitor (rat amylin).
3 mposed of islet amyloid polypeptide (IAPP or amylin).
4 gation of islet amyloid polypeptide (IAPP or amylin).
5 uggest novel (to our knowledge) findings for amylin.
6 shares three proline substitutions with rat amylin.
7 ats, and in AKO rats infused with aggregated amylin.
8 able to seed amyloid formation by unmodified amylin.
9 n (HDL), leptin, pancreatic polypeptide, and amylin.
10 ificantly more effective inhibitors than rat amylin.
11 hairpin loop by the single disulfide bond in amylin.
12 may respond to a combination of leptin plus amylin.
13 f peptides that require RAMPs; CGRP, AM, and amylin.
14 of-action mediating the anorectic effects of amylin.
15 association with the -HSSNN- residues of the amylin.
17 ession of these genes yields a high-affinity amylin-1 receptor (AMY1-R)], with highest overlap in the
21 upregulation of IAPP, the gene that encodes amylin, a 37-amino-acid peptide co-secreted with insulin
23 s expressing the same level of wild-type rat amylin, a nonamyloidogenic isoform, exhibited normal hea
26 irculating levels of amylin may also lead to amylin accumulation and proteotoxicity in peripheral org
34 ures, but it is not known whether pancreatic amylin affects amyloid pathogenesis in the AD brain.
35 e inhibitory effect of the copper(II) ion on amylin aggregation has been recently discovered, but det
39 both nonclinical and clinical evidence that amylin agonism restored leptin responsiveness in diet-in
40 hermore, the presence of a disulfide bond in amylin allows IDE to cut at an additional site in the mi
43 CTR-like receptor (CLR) for calcitonin (CT), amylin (Amy), calcitonin gene-related peptide (CGRP), an
45 disorders and aging promote accumulation of amylin amyloid in the cerebrovascular system and gray ma
47 human islet amyloid polypeptide (hIAPP, aka amylin), an amyloidogenic peptide associated with beta-c
48 e 2 diabetes and dementia have deposition of amylin, an amyloidogenic hormone cosecreted with insulin
49 stration of recombinant human leptin and the amylin analog pramlintide elicited 12.7% mean weight los
50 ssive effects of a peripherally administered amylin analog, suggesting that amylin receptor signaling
52 asma samples, a positive association between amylin and Abeta1-42 as well as Abeta1-40 is found only
54 AKO rats of human amylin, or combined human amylin and apolipoprotein E4, showed that amylin binds t
55 f appetite induced by the anorectic hormones amylin and cholecystokinin, as well as by lithium chlori
56 mouse models, we investigated the effects of amylin and its clinical analog, pramlintide, on AD patho
57 efficient inhibition of amyloid formation of Amylin and its disruption by a novel class of conformati
60 udies also show that the amyloidogenicity of amylin and its processing intermediates is negatively co
61 that concurrent peripheral administration of amylin and leptin elicits synergistic, fat-specific weig
62 tructural basis for the interactions between amylin and membranes, we determined the NMR structure of
72 ct was associated with higher serum insulin, amylin, and glucagon-like peptide 1 levels compared with
73 cortisolaemia; decreases in leptin, insulin, amylin, and incretins; and increases in ghrelin, peptide
76 are thought to facilitate the aggregation of amylin, and membrane-bound oligomers may be responsible
79 se used for Abeta, the fibrillar assembly of amylin, another amyloidogenic peptide, was not inhibited
80 folded and random-coil conformations of rat amylin are observed in water and their relative stabilit
81 et amyloid polypeptide (hIAPP, also known as amylin) as islet amyloid is a characteristic feature of
84 jury, generating reactive aldehydes, forming amylin-based adducts with reactive aldehydes, and increa
88 the densest concentrations of high-affinity amylin binding; nevertheless, these receptors have not b
94 ose that detection and disruption of cardiac amylin buildup may be both a predictor of heart dysfunct
98 ay play a role in regulating Abeta in brain, amylin class peptides may provide a new avenue for both
101 Using LAESI-IMS-MS for the assessment of amylin-copper(II) interactions demonstrates the utility
103 or eight-saccharide monomers protect against amylin cytotoxicity toward a MIN6 mouse cell model of pa
104 itively charged N-terminal half of monomeric amylin depends on the concentration of negatively charge
105 mmon in individuals with prediabetes, causes amylin deposition and proteotoxicity in pancreatic islet
106 INTERPRETATION: These data identify vascular amylin deposition as a trigger of brain endothelial dysf
110 are consistent with the pathological role of amylin deposition in the pancreas, uncover a novel contr
116 We tested the hypothesis that the vascular amylin deposits cause endothelial dysfunction and microv
123 amidation together with structural models of amylin fibers reveals that deamidation in the N-terminal
127 CreateFibril constructed HET-s, Abeta, and amylin fibrils up to 17 nm in length, and utilized a nov
128 iments indicate that heparin associates with amylin fibrils, rather than enhancing fibrillogenesis ca
130 ely, on membranes incorporating cholesterol, amylin formed highly compact approximately 200- to 500-n
131 On cholesterol-depleted planar membranes, amylin formed highly symmetrical tetrameric and pentamer
132 ture secretory granule (37 degrees C, pH 6), amylin forms amyloid aggregates more rapidly than its pr
134 urally homogeneous fibrils from a 30-residue amylin fragment (hIAPP 8-37) produces morphologically ho
136 involved in this tumour regression and that amylin functions through the calcitonin receptor (CalcR)
137 ary evaluation by more than twofold, whereas amylin greater than or equal to 116 pg/ml decreased the
140 ated amyloidogenic systems, human pancreatic amylin (hAM) and alpha-synuclein (alpha-syn), associated
142 mbrane by the amyloidogenic peptide IAPP (or amylin) has been implicated in beta-cell death during ty
143 let Amyloid Polypeptide (IAPP, also known as amylin) has been shown to disrupt beta-cell membranes le
145 ormed by the amyloidogenic fragment of human amylin hIAPP20-29 subjected to force applied in a variet
149 y observed differences between human and rat amylin in solution and their possible relation to aggreg
151 ttle is known, however, about the effects of amylin in the nucleus accumbens shell (AcbSh), where a c
152 Rats overexpressing amyloidogenic (human) amylin in the pancreas (HIP rats) and amylin knockout (A
154 stable, soluble random-coil conformation for amylin in the presence of cholesterol that could explain
159 One intracerebroventricular injection of amylin induces a more significant surge in serum Abeta t
162 elf-assembly of the human pancreatic hormone amylin into toxic oligomers and aggregates is linked to
166 nderpinning T2D, but that amyloidogenesis of amylin is closely involved, we have been seeking to unde
168 In patients afflicted with type 2 diabetes, amylin is found in fibrillar deposits in the pancreas.
169 monomer of the human, amyloidogenic form of amylin is more compact than the rat form, which does not
173 Human islet amyloid polypeptide (hIAPP or Amylin) is a 37 residue hormone that is cosecreted with
177 Human islet amyloid polypeptide (hIAPP or amylin) is a causative agent in pancreatic amyloid depos
179 let amyloid polypeptide (IAPP; also known as amylin) is responsible for islet amyloid formation in ty
182 et amyloid polypeptide (IAPP), also known as amylin, is responsible for amyloid formation in type 2 d
183 wledge, that the N-terminal loop (N_loop) of amylin (islet amyloid polypeptide (IAPP) residues 1-8) f
185 f calcitonin-gene-related peptide (CGRP) and amylin (islet amyloid polypeptide, IAPP), two intrinsica
186 ha-synuclein (aS) forms amyloids and in T2D, amylin [islet amyloid polypeptide (IAPP)] forms amyloids
187 human) amylin in the pancreas (HIP rats) and amylin knockout (AKO) rats intravenously infused with ag
189 ological conditions that augment insulin and amylin levels, such as oral glucose administration, acut
190 ion with NTE-1 did result in elevated plasma amylin levels, suggesting the in vivo role of IDE action
191 However, elevated circulating levels of amylin may also lead to amylin accumulation and proteoto
192 suggesting the in vivo role of IDE action on amylin may be more significant than an effect on insulin
193 Recent evidence suggests that both Abeta and amylin may express their effects through the amylin rece
195 We therefore hypothesized that oligomerized amylin might accumulate in the cerebrovascular system an
197 port the conformational preferences of human amylin monomer in solution using molecular simulations a
200 dition of water-soluble cholesterol restores amylin oligomer clustering at the PM and internalization
201 nsulin-resistant patients, is known to cause amylin oligomerization and cytotoxicity in pancreatic is
203 icroscopy reveals an increased nucleation of amylin oligomers across the plasma membrane in cholester
206 ransgenic for human amylin, we observed that amylin oligomers attach to the sarcolemma, leading to my
207 ition, sorting, and internalization of toxic amylin oligomers but not monomers in pancreatic rat insu
208 Biochemical studies confirm accumulation of amylin oligomers in the medium after depletion of PM cho
210 We found significant accumulation of large amylin oligomers, fibrils, and plaques in failing hearts
211 hanism for selective uptake and clearance of amylin oligomers, impairment of which greatly potentiate
212 skeleton network inhibits internalization of amylin oligomers, which in turn enhances extracellular o
214 dynamics and macromolecular organization of amylin on anionic and neutral planar membranes that lack
217 is orientation may direct the aggregation of amylin on membranes, whereas coupling between the two se
219 l (i.p.) injection of AD animals with either amylin or pramlintide reduces the amyloid burden as well
220 Intravenous infusion in AKO rats of human amylin, or combined human amylin and apolipoprotein E4,
223 ls formed by other polypeptides, such as the amylin peptide associated with type 2 diabetes, these st
224 The 37-residue, C-terminally amidated human amylin peptide derives from a proprotein that undergoes
228 ptide-1 receptor agonist, exenatide (Byetta, Amylin Pharmaceuticals, CA) has properties that could im
230 e have examined the effect of cholesterol on amylin polymerization both on planar membranes and in so
231 lain the inhibitory effect of cholesterol on amylin polymerization in solution and on membranes.
232 logical consequence of cholesterol-regulated amylin polymerization on membranes and biochemical mecha
236 The pancreatic- and brain-derived hormone amylin promotes negative energy balance and is receiving
239 cbSh), where a circumscribed zone of intense amylin receptor (AMY-R) binding overlaps reported mappin
246 nist studies provide novel evidence that VTA amylin receptor blockade increases food intake and atten
249 We show that mRNA for all components of the amylin receptor complex is expressed in the ventral tegm
251 administered amylin analog, suggesting that amylin receptor signaling in the VTA is physiologically
252 ral knockdown experiments indicate that LDTg amylin receptor signaling is physiologically and potenti
253 amylin may express their effects through the amylin receptor, although the precise mechanisms for thi
255 immunohistochemical data indicate that LDTg amylin receptors are expressed on gamma-aminobutyric aci
260 reversed DAMGO-induced hyperphagia; 3 ng of amylin reduced DAMGO-mediated feeding by nearly 50%.
261 e cleavage sites of human IGF-II, TGF-alpha, amylin, reduced amylin, and amyloid-beta by human IDE.
263 (29) of the human islet amyloid polypeptide amylin, reveals that the peptide assembles into two amyl
265 rier, our study demonstrates that peripheral amylin's action on the central nervous system results in
267 leus with therapeutic potential in mediating amylin's effects on energy balance through gamma-aminobu
269 ormones released following a meal, including amylin, secreted by the pancreas, and cholecystokinin (C
273 g throughout the brain, the possible role of amylin signaling at other nuclei in the control of food
275 expressing endogenous (nonamyloidogenic) rat amylin, studied normal mice injected with aggregated hum
276 of the processing intermediates relative to amylin suggests their presence in intracellular amyloid
279 Pramlintide is a synthetic analog of human amylin that shares three proline substitutions with rat
281 -specific structure for the complex of human amylin (the peptide responsible for islet amyloid format
282 ng such system is islet amyloid polypeptide (Amylin), the causative agent of amyloid formation in typ
283 of the human islet amyloid protein (hIAPP or amylin), the protein associated with type II diabetes.
285 ntagonist for AMY1-R, blocked the ability of amylin to normalize AMPH-induced PPI disruption, showing
289 nd microvascular injury and are modulated by amylin transport in the brain via plasma apolipoproteins
292 production is the likely mechanism by which amylin treatment interacts with VMH leptin signaling to
293 -1beta might function as a sensor of myocyte amylin uptake and a potential mediator of myocyte injury
294 present detailed solution structures of rat amylin using a combination of Monte Carlo and molecular
296 odel of hyperamylinemia transgenic for human amylin, we observed that amylin oligomers attach to the
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